Not Applicable.
Reference to a xe2x80x9cComputer Listing Appendix submitted on a Compact Discxe2x80x9d
Not Applicable.
(1) Field of the Invention
The present invention relates to an osmium-assisted process for the oxidative cleavage of oxidizable organic compounds such as unsaturated organic compounds, including alkenes and olefins into aldehydes, carboxylic acids, esters, or ketones. The process uses a metal catalyst comprising osmium and a peroxy compound selected from the group consisting of peroxymonosulfuric acid and salts thereof to oxidatively cleave the oxidizable organic compound. In particular, the process enables aldehydes, carboxylic acids, esters, or ketones to be selectively produced from the corresponding mono-, 1,1-di-, 1,2-di-, tri-, or tetra-substituted olefins in a reaction that produces the result of ozonolysis but with fewer problems. The present invention further provides a process for oxidizing an aldehyde alone or with the osmium in an interactive solvent to produce an ester or carboxylic acid.
(2) Description of Related Art
In organic synthesis, oxidations and reductions are the key reactions for organic chemists. In particular, oxidative processes are essential components to the success of organic synthesis. Such processes include (1) metal assisted oxidative cleavage of alkenes (potassium permanganate) (Arney et al,. J. Org. Chem. 58: 6126xe2x80x946128 (1993); Lee et al., J. Org. Chem. 44: 2726xe2x80x942730 (1979)), (2) oxidative cleavage of diols (sodium periodate) (Gupta et al., J. Chem. Soc._Perkin Trans. 1: 2970xe2x80x942973 (1981); Schmid et al., J. Org. Chem. 56: 4056xe2x80x944058 (1991); Price et al., J. Am. Chem. Soc. 64: 552xe2x80x94554 (1942)), and (3) ozonolysis (Hon et al., Tetrahedron Lett. 34: 6591xe2x80x946594 (1993); Schreiber et al., Tetrahedron Lett. 23: 3867xe2x80x943870 (1982); Schreiber et al., J. Am. Chem. Soc. 110: 6210xe2x80x946218 (1988)).
While numerous oxidative and reductive processes have been reported in the prior art, when it comes to cleaving or oxidizing carbonxe2x80x94carbon double bonds in oxidizable organic compounds to form aldehydes, ketones, carboxylic acids, or esters, there are two primary processes for cleaving the organic compounds, either (i) transform the organic compound into a 1,2-diol followed by cleavage with NaIO4 or similar oxidant, or (ii) ozonolysis which transforms the organic compound into a variety of symmetrically or desymmetrically functionalized products depending on the workup conditions.
There are processes for oxidatively cleaving olefins such as oxidative cleavage of diols and ozonolysis, however, while these processes have specific advantages, they also have serious drawbacks. For example, potassium permanganate (KMnO4) is a cheap and useful oxidant, but it is not soluble in many organic solvents and it is often non_specific, which means that undesired oxidations occur during the oxidation which makes the workup tedious (Viski et al., J. Org. Chem. 51: 3213xe2x80x943214 (1986)). In particular, permanganate is not a selective oxidant; thus, there are many possible side reactions in processes that use KMnO4 (Lee et al., J. Am. Chem. Soc. 105: 3188xe2x80x943191 (1983)). Therefore, much of the work in the area of oxidative cleavage of alkenes using permanganate has been focused on the use of various phase transfer catalysts and solid supported reagents (Harris et al., Tetrahedron Lett. 38: 981xe2x80x94984 (1997); Ferreira et al., J. Org. Chem. 52: 3698xe2x80x943699 (1987); Clark et al., J. Chem. Soc._Chem. Commun., 635xe2x80x94636 (1982); Noureldin et al., Tetrahedron Lett. 22: 4889xe2x80x944890 (1981); Lee et al., J. Org. Chem. 58: 2918xe2x80x942919 (1993)) to modify the reactivity and selectivity of the permanganate, but while these reactions are milder and more selective than permanganate itself, this has not proved to be a general solution to the problem.
Sodium periodate (NaIO4) is another useful reagent for cleaving diols. This reagent is also limited by its insolubility in organic solvents (Schmid et al., J. Org. Chem. 56: 4056xe2x80x944058 (1991)). To increase the solubility and reactivity of the oxidant, processes have been developed that use quaternary alkyl ammonium periodate (Santaniello et al., Tetrahedron Lett. 21: 2655xe2x80x942656 (1980); Keck et al., Tetrahedron Lett. 78: 4763xe2x80x944766 (1978)), potassium metaperiodate along with phase transfer catalysts (Kalsi et al., Chem. Ind., 394xe2x80x94395 (1987)), and silica gel supported NaIO4 (Daumas et al., Synthesis, 64xe2x80x9465 (1989)). While these modifications have to some extent been successful, the primary drawback of these modified reactions is that it is necessary to convert the carbon double bond to a diol before it can be cleaved. As an alternative, catalytic osmium tetroxide (OsO4) and NaIO4 have been used together to oxidatively cleave olefins in a one pot process (Cainelli et al., Synthesis, 47xe2x80x9448 (1989)). However, this reaction often produces undesirable byproducts. To reduce the production of undesirable byproducts, the diol precursor is prepared in a separate reaction which is then used in a second periodate cleavage reaction to produce the cleavage product. Therefore, the process is still a two step process instead of the more desirable one pot process. Furthermore, other 1,2_diols within target molecules needs to be protected from oxidative cleavage.
The over-oxidation pathway, providing xcex1-hydroxy ketones, aldehydes, and carboxylic acids, is seldom described in literature for osmium tetroxide without the use of NaIO4. OsO4 is much better known for formation of 1,2-diols (Shroder, Chem. Rev. 80: 187-213 (1980); Gobel et al., Angew. Chem.-Intl. Ed. Engl. 32: 1329-1331 (1993); Ogino et al., Tetrahedron Lett. 32: 3965-3968 (1991)) by hydrolysis of an intermediate osmate ester. Classically, conditions that usually promote higher levels of over-oxidation include catalytic OsO4 with hydrogen peroxide (Milas et al., J. Am. Chem. Soc. 81: 4730-4733 (1959)) or tert-butyl hydrogen peroxide (Sharpless et al., J. Am. Chem. Soc. 22: 1287-1290 (1976)) as co-oxidants.
U.S. Pat. No. 3,946,065 to Matsui et al. discloses that a combination agent such as osmium tetroxide-sodium periodate or potassium permanganate-sodium periodate can be used to oxidize bicycloheptene to bicyclopentane. Also disclosed is a two-step process for cleaving the double bond of bicycloheptene by oxidizing the double bond to a vicinal alcohol using osmium tetroxide or peracid and then oxidizing the resulting single carbon bond with periodic acid or its metal salts, lead tetraacetate, a manganese compound, or a chromium compound.
In the prior art, the standard process for oxidative cleavage of olefins is ozonolysis. This reaction has been well_developed and yields aldehydes or carboxylic acids upon reductive or oxidative workup, respectively (Schreiber et al., Tetrahedron Lett. 23: 3867xe2x80x943870 (1982)). Desymmetrization of the carbonyl functionality upon cleavage of cyclic olefins is also possible through the use of interactive solvents that yield an ester and an aldehyde (Hon et al., Tetrahedron Lett. 34: 6591xe2x80x946594 (1993); Schreiber et al., J. Am. Chem. Soc.110: 6210xe2x80x946218 (1988)).
Ozonolysis is a unique reaction that enables the cleavage of double-bonded carbons with ozone to yield aldehydes, carboxylic acids, or esters, which are then used as starting materials for producing a variety of important organic compounds. Ozonolysis is used by the petroleum industry to process crude oil into many small pure organic molecules, which are then used to make a variety of petrochemical products. While ozonolysis of crude oil is the primary commercial process for producing these important organic compounds, many of the ozonolysis reactions are low yielding. Furthermore, ozonolysis is an inherently dangerous process. The ozonides produced during ozonolysis are particularly dangerous and pose the risk of explosion. Therefore, an alternative reaction that is able to perform in a manner similar to ozonolysis would be highly desirable.
As important as ozonolysis has proved to be in synthetic chemistry, there are no alternative reactions that duplicate the same transformation. Therefore, in reactions where the conditions in which the ozonolysis is to be performed are not tolerated by the olefin, the choice for cleaving the olefin is usually by oxidation of 1,2_diols. A significant problem with ozonolysis is safety. Ozonides generated during ozonolysis are particularly dangerous and serious accidents due to explosions have been reported (Ogle et al., Process Saf. Prog. 17: 127xe2x80x94133 (1998); Koike et al., Chem. Eng. Jpn. 32: 295xe2x80x94299 (1999); Dorofeev et al., Doklady Akademii NauK SSSR 257: 592xe2x80x94596 (1981); Gershenzon et al., High Energy Chem. 11: 218xe2x80x94222 (1977); Gershenzon et al., Kinet. Catal. 18: 1284xe2x80x941287 (1977)). Therefore, there is a need for a process for cleaving olefins that uses a reaction that produces the results of ozonolysis but without the drawbacks associated with ozonolysis.
The present invention provides a process for producing carboxylic acids, ketones, or esters from olefins in an osmium-assisted reaction that produces the result of ozonolysis but without the problems associated with ozonolysis. The process is both efficient and inexpensive. The primary elements that make the process of the present invention more advantageous than the processes of the prior art is that (i) the diol intermediate is no longer formed as with the alternative metal-assisted cleavage methodologies, (ii) the process does not require an elaborate setup such as is required for the production of ozone to be used in the ozonolysis, (iii) the reaction is mild and can be performed under a variety of conditions, and (iv) the intermediates formed during the reaction do not pose the risk of explosion. Unexpectedly, it was discovered that the process was versatile in terms of both the oxidation state of the organic compound produced and the functional groups of the substrate that are tolerated.
Therefore, the present invention provides an osmium-assisted process for the oxidative cleavage of oxidizable organic compounds such as unsaturated organic compounds, including alkenes and olefins into aldehydes, carboxylic acids, esters, or ketones. The process uses a metal catalyst comprising osmium and a peroxy compound selected from the group consisting of peroxymonosulfuric acid and salts thereof to oxidatively cleave the oxidizable organic compound. In particular, the process enables aldehydes, carboxylic acids, esters, or ketones to be selectively produced from the corresponding mono-, 1,1-di-, 1,2-di-, tri-, or tetra-substituted olefins in a reaction that produces the result of ozonolysis but with fewer problems. The present invention further provides a process for oxidizing an aldehyde alone or with the osmium in an interactive solvent to produce an ester or carboxylic acid.
Thus, the present invention provides a process for oxidative cleavage of an oxidizable organic compound to form an oxidized organic compound which comprises reacting the oxidizable organic compound with a mixture of a metal catalyst comprising osmium and a peroxy compound selected from the group consisting of peroxymonosulfuric acid and salts thereof which oxidatively cleaves the oxidizable organic compound to form the oxidized organic compound.
The present invention further provides a process for oxidative cleavage of an oxidizable organic compound to form an oxidized organic compound which comprises reacting the oxidizable organic compound with a mixture of a metal catalyst comprising osmium and an alkali metal monopersulfate which oxidatively cleaves the oxidizable organic compound to form the oxidized organic compound.
In a particular embodiment of the process, the alkali metal is potassium. In a further embodiment, the oxidizable organic compound contains unsaturated bonds which are oxidized, in particular, wherein the bonds are double bonds. In a further embodiment, the reaction is performed in a non-oxidizable organic solvent. In a further embodiment, the osmium is selected from the group consisting of osmium tetroxide (OsO4), osmium trichloride (OsCl3), K2OsO4*2H2O, and mixtures thereof.
Further still, the present invention provides a process for oxidizing a carbonxe2x80x94carbon double bond in an organic compound to produce an organic compound selected from the group consisting of an aldehyde, ketone, carboxylic acid, and ester, comprising (a) providing the organic compound with the carbonxe2x80x94carbon double bond in an organic solvent; (b) reacting the organic compound with the carbonxe2x80x94carbon double bond in the organic solvent with a mixture of a metal catalyst comprising osmium and an oxidizing compound selected from the group consisting of peroxymonosulfuric acid and salts thereof in a reaction wherein the carbonxe2x80x94carbon double bond is oxidized to produce the organic compound selected from the group consisting of an aldehyde, ketone, carboxylic acid, and ester; and (c) recovering the organic compound selected from the group consisting of the aldehyde, ketone, carboxylic acid, and ester from the reaction.
In a further embodiment, the osmium is selected from the group consisting of osmium tetroxide (OsO4), osmium trichloride (OsCl3), K2OsO4*2H2O, and mixtures thereof. Further still, the metal catalyst is provided in a polymer. In a preferred embodiment, the oxidizing compound is an alkali metal peroxymonosulfate, in particular, wherein the alkali metal peroxymonosulfate is potassium peroxymonosulfate or wherein the oxidizing compound comprises 2 KHSO5.KHSO4.K2SO4, known by the trade name OXONE.
In a further embodiment, the organic solvent is selected from the group consisting of dimethyl formamide, dichloromethane, methanol, ethanol, propanol, butanol, N-methyl pyrrolidinone, hexamethyl phosphonamide, pyrrolidinone, dimethyl acetomide, and acetone. The alcohols react with the organic acids to form esters.
In an embodiment further still, the organic compound with the carbonxe2x80x94carbon double bond is an olefin, in particular, wherein the olefin is selected from the group consisting of mono-substituted, 1,1_di-substituted, 1,2_di-substituted, tri-substituted, tetra-substituted olefins, and mixtures thereof.
The present invention also provides a composition for use in oxidizing organic compounds which comprises in admixture (a) a metal catalyst comprising osmium; and (b) a peroxy compound selected from the group consisting of peroxymonosulfuric acid and salts thereof.
In a further embodiment, the peroxy compound is an alkali metal peroxymonosulfate, in particular, wherein the alkali metal is potassium. In a further embodiment, the composition is used in a non-oxidizable organic solvent in the process. In a further embodiment, the osmium is selected from the group consisting of osmium tetroxide, osmium trichloride, K2OsO4*2H2O, and mixtures thereof Further still, the present invention provides a composition for use in oxidizing an olefin to an aldehyde, ketone, carboxylic acid, or ester which comprises in admixture (a) a metal catalyst comprising osmium; and (b) an oxidizing compound selected from the group consisting of peroxymonosulfuric acid and salts thereof.
In a further embodiment, the osmium is selected from the group consisting of osmium tetroxide (OsO4), osmium trichloride (OsCl3), K2OsO4*2H2O, and mixtures thereof. Further still, the metal catalyst is provided in a polymer.
In a further embodiment, the oxidizing compound is an alkali metal peroxymonosulfate, in particular, wherein the alkali metal peroxymonosulfate is potassium peroxymonosulfate or wherein the oxidizing compound comprises 2 KHSO5.KHSO4.K2SO4.
The present invention also provides a kit as a package for use in oxidizing an organic compound which comprises (a) a first container of a metal catalyst comprising osmium; and (b) a second container of a peroxy compound selected from the group consisting of peroxymonosulfuric acid and salts thereof.
In a further embodiment, the peroxy compound is an alkali metal peroxymonosulfate, in particular, wherein the alkali metal is potassium.
In a further embodiment, the first and second containers contain a non-oxidizable solvent.
In a further embodiment, the osmium is selected from the group consisting of osmium tetroxide (OsO4), osmium trichloride (OsCl3), K2OsO4*2H2O, and mixtures thereof.
In a further embodiment, the present invention provides a process for producing an ester from an aldehyde comprising (a) providing the aldehyde in an alcohol solvent; (b) reacting the aldehyde and the alcohol solvent with an oxidizing compound selected from the group consisting of peroxymonosulfuric acid and salts thereof alone or with an additional oxidant in a reaction wherein the aldehyde is oxidized and which reacts with the alcohol solvent to form the ester; and (c) recovering the ester from the reaction.
In a further embodiment of the process, the oxidizing compound is an alkali metal peroxymonosulfate, preferably wherein the alkali metal peroxymonosulfate is potassium peroxymonosulfate or wherein the oxidizing compound comprises 2 KHSO5.KHSO4.K2SO4. Preferably, the alcohol is a lower alcohol and most preferably, the alcohol is selected from the group consisting of methanol, ethanol, propanol, and butanol; however, numerous other alcohols can be used.
In a further embodiment, the additional oxidant is a metal catalyst comprising osmium, preferably the osmium is selected from the group consisting of osmium tetroxide (OsO4), osmium trichloride (OsCl3), K2OsO4*2H2O, and mixtures thereof.
The present invention further provides a process for producing a carboxylic acid from an aldehyde comprising (a) providing the aldehyde in a solvent selected from the group consisting of dimethyl formamide, dichloromethane, methanol, ethanol, propanol, butanol, N-methyl pyrrolidinone, hexamethyl phosphonamide, pyrrolidinone, dimethyl acetomide, and acetone; (b) reacting the aldehyde with an oxidizing compound selected from the group consisting of peroxymonosulfuric acid and salts thereof alone or with an additional oxidant in a reaction wherein the aldehyde is oxidized to the acid; and (c) recovering the acid from the reaction.
Preferably, the oxidizing compound is an alkali metal peroxymonosulfate or a soluble form of OXONE. In particular, wherein the alkali metal peroxymonosulfate is potassium peroxymonosulfate. Most preferably, the oxidizing compound comprises 2 KHSO5.KHSO4.K2SO4.
In a further embodiment, the additional oxidant is a metal catalyst comprising osmium, preferably the osmium is selected from the group consisting of osmium tetroxide (OsO4), osmium trichloride (OsCl3), K2OsO4*2H2O, and mixtures thereof.
Objects
It is an object of the present invention to provide a process for oxidizing an organic compound to produce an oxidized product in a reaction that produces the results of ozonolysis without having the drawbacks of ozonolysis.
In particular, it is an object of the present invention to provide a process for producing carboxylic acids, ketones, aldehydes, or esters from olefins in a reaction that produces the results of ozonolysis without having the drawbacks of ozonolysis.
It is further an object of the present invention to provide a process for producing esters from aldehydes.
These and other objects of the present invention will become increasingly apparent with reference to the following drawings and preferred embodiments.